The overall objective is to investigate effects of long-term treatment with amitriptyline (a drug representative of the tricyclic antidepressants), and thoridazine (a drug representative or the antipsychotic drugs) on secretory activities ( salivary flow, ion concentrations such as Na, K and Ca and amylase activity) of rat salivary glands in response to autonomic and autonomimetic stimulation. Although the mechanisms of actions of tricyclic antidepressants or antipsychotic drugs on brain have been extensively investigated, the actions of their side effect (dry mouth) have been largely ignored. Xerostomia is an important problem of veterans who are regularly taking antidepressants or antipsychotic drugs because this oral dryness can often interfere with medical management and can predispose to oral symptoms and diseases. Thus, the effects of chronic administration of amitriptyline and thioridazine on secretory activities of rat parotid and submandibular glands in response to electrical stimulation of both branches of the autonomic nervous system as well as autonomic agonist stimulation will be examined. The mechanisms by which amitriptyline and thioridazine induce changes in secretory activities of rat salivary glands, e.g., changes in muscarinic cholinergic and beta-adrenergic receptor binding also will be investigated. The extent to which salivary gland function returns to normal (if at all) when the drug treatment is discontinued, and the time it takes to do so, will be determined. The effects of Sialor, a synthetic sialogogue, on the secretory activities of salivary glands of rats chronically treated with amitriptyline or thioridazine will be evaluated. The proposed research should provide a better understanding of the mechanisms of actions of amitriptyline and thioridazine on salivary glands. It would also provide information regarding the beneficial effect of a pharmacologic agent, Sialor, in antagonizing drug-induced changes in salivary gland function.